DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Application
Receipt of the Preliminary Amendment filed on April 25, 2024 is acknowledged.
Receipt of Applicant’s response filed on November 25, 2025 is acknowledged. Claims 1-13, 15-16, 19-24 are pending in this application.
Claims 14 and 17-18 have been cancelled.
Claims 1-13 and 15-16 have been amended.
Claims 19-24 are new.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-8 and 19-21) in the reply filed on November 25, 2025 is acknowledged.
Claims 9-13, 15-16, and 22-24 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Groups II-IV, there being no allowable generic or linking claim.
Therefore, claims 1-8 and 19-21 are under examination in this application.
Claim Objections
Claims 1, 5, and 7 are objected to because of the following informalities:
Regarding claim 1, the claim contains an unnecessary comma (,) after “layer”.
Regarding claim 5, the claim depends from claim 1, however recites the mucoadhesive layer comprises the “non-nanoparticulate macrolide”, however, claim 1 recites the mucoadhesive layer comprises a non-nanoparticulate macrolide. Therefore, the additional recitation is redundant. It is suggested the claim be amended to recite “The mucoadhesive layer according to claim 1, further comprising:
a mucoadhesive polymer;
a cellulose derivative;
a plasticizer; and
optionally a colorant.”
Regarding claim 7, the claim does not read well, it is suggested the claim be amended to recite “The mucoadhesive layer according to claim 1, further comprising:
a mucoadhesive polymer that is an amphiphilic polymer, hydroxypropyl cellulose (HPC), carboxymethyl cellulose (CMC), a plasticizer, and optionally a colorant; or
a mucoadhesive polymer selected from the group consisting of crosslinked polyacrylic acid polymers and copolymers of methyl vinyl ether and maleic anhydride; hydropropyl cellulose (HPC); ethyl cellulose (EC); a plasticizer; optionally a colorant.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 19 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 19 recites the limitation "the macrolide immune suppressant", “the macrolide antibiotic”, and “the macrolide antifungal” in lines 2, 4, and 7, respectively. There is insufficient antecedent basis for these limitations in the claim. Claim 1, from which 19 depends recites “a non-nanoparticulate macrolide”.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-3, 5-6, 8, and 19-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ashwathy et al. (Development and Chacterization of Buccal Film: Tacrolimus as a model drug, Journal of Medical Biomedical and Applied Sciences, 21 January 2019).
Ashwathy discloses mucoadhesive buccal film drug delivery of tacrolimus (abstract). Chitosan and HPMC were dissolved in a diluted acetic acid and distilled water solution. Tacrolimus was then added by dissolving the drug in a small quantity of ethanol. The mixture was then stirred and casted (Development of Tacrolimus film formulation). The tacrolimus is therefore dissolved and is considered non-nanoparticulate.
Regarding claims 2 and 19, as noted above, tacrolimus is disclosed. Tacrolimus is a macrolide immune suppressant.
Regarding claim 3, as noted above, the tacrolimus is dissolved.
Regarding claims 5-6 and 20, formulation F2 in table 1 discloses the film comprises tacrolimus (a macrolide); chitosan (a mucoadhesive polymer), HPMC ( a cellulose derivative), and polypropylene glycol (a plasticizer), as noted above, HPMC, a cellulose derivative was dissolved in acetic acid solution (an organic solvent).
Regarding claim 8, formulation F2 comprises 2.7% tacrolimus (Table 1).
Ashwathy, therefore, anticipates the rejected claims.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-5 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over McClain et al. (CA 2810842) in view of Kaurav et al. (Mucoadhesive Microspheres as carriers in Drug Delivery: a Review, International Journal of Drug Development and Research, April-June 2012, Vol 4, Issue 2).
McClain discloses macrolide dosage forms comprising at least one polymer and at least one active agent (abstract). In one embodiment, the biologically active agent (macrolide) can be encapsulated in microparticles (paragraph 0012). Regarding the recitation of "non-nanoparticulate macrolide", the instant specification states that "non-nanoparticulate macrolide" relates to the macrolide that is not formulated as nanoparticles, particularly not formulated as nanoparticles having a size in the range of 1 nm to 1000 nm. "Micronized" crystalline macrolide has an average particle size of greater than 1000 nm(pg.11, lines 17-20, lines 29-30). Based on such statements, the Examiner interprets the term "non-nanoparticulate macrolide" to mean macrolide having average particle size of greater than 1000 nm.
Mucoadhesive properties are provided by a bioabsorbable polymer (paragraph 0027).
Regarding claims 2 and 19, rapamycin, sirolimus, everolimus, zotarolimus, and biolimus are disclosed (paragraph 0016).
Regarding claim 3, as noted above, the particles can be microparticles.
McClain does not disclose the particle size of the macrolide formulation.
Kaurav discloses microspheres constitute an important part of novel drug delivery systems by virtue of their small size and efficient carrier capacity. Due to their short residence time, bioadhesive characteristics can be coupled to microspheres to develop mucoadhesive microspheres. Microsphere particles range from 1-1000 mm in diameter having a core of drug and entirely outer layers of polymer as coating material (abstract).
Regarding claim 4, as noted above, microsphere particles range from 1 to 1000 mm.
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the invention to have prepared the formulation of McClain as microparticles since Kaurav discloses mucoadhesive microspheres have advantages life efficient absorption and enhanced bioavailability of the drugs due to a high surface to volume ratio, a much more intimate contact with the mucus layer, controlled and sustained release of drug from the dosage form and specific targeting of drugs to the absorption site.
Claim 7 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Ashwathy et al. (Development and Chacterization of Buccal Film: Tacrolimus as a model drug, Journal of Medical Biomedical and Applied Sciences, 21 January 2019) in view of Nadh et al. (An Overview on Mucoadhesive Polymers for Buccal Drug Delivery, Int. J. Pharm. Sci. Rev. Res., 67(1), March-April 2021, Article No. 29, pages 178-186).
The teachings of Ashwathy are discussed above. As noted above, formulation F2 in table 1 discloses the film comprises tacrolimus (a macrolide); chitosan (a mucoadhesive polymer), HPMC ( a cellulose derivative), and polypropylene glycol (a plasticizer), as noted above, HPMC, a cellulose derivative was dissolved in acetic acid solution (an organic solvent).
Ashwathy does not disclose the mucoadhesive layer components as recited in claims 7 and 21.
Nadh discloses buccal drug delivery refer specifically to the provision of medications within or through the oral mucosa, which affect pharmaceutical products delivered through the buccal route can be used for the treatment of oral or systemic diseases in cavity (introduction).
Mucoadhesive polymers are water-insoluble and water soluble polymers connected by crosslinking agents, which are swellable networks. Examples of water soluble mucoadhesive polymers include HPC, HPMC, CMC, and PAA (classification of mucoadhesive polymers).
The person of ordinary skill in the art is a hypothetical person who is presumed to have known the relevant art at the relevant time. Factors that may be considered in determining the level of ordinary skill in the art may include: (A) "type of problems encountered in the art;" (B) "prior art solutions to those problems;" (C) "rapidity with which innovations are made;" (D) "sophistication of the technology; and" (E) "educational level of active workers in the field. In a given case, every factor may not be present, and one or more factors may predominate." In re GPAC, 57 F.3d 1573, 1579, 35 USPQ2d 1116, 1121 (Fed. Cir. 1995); Custom Accessories, Inc. v. Jeffrey-Allan Indus., Inc., 807 F.2d 955, 962, 1 USPQ2d 1196, 1201 (Fed. Cir. 1986); Environmental Designs, Ltd. V. Union Oil Co., 713 F.2d 693, 696, 218 USPQ 865, 868 (Fed. Cir. 1983).
"A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton." KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 421, 82 USPQ2d 1385, 1397 (2007). "[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle." Id. at 420, 82 USPQ2d 1397. Office personnel may also take into account "the inferences and creative steps that a person of ordinary skill in the art would employ." Id. at 418, 82 USPQ2d at 1396.
It would have obvious to one of ordinary skill in the art prior to the effective filing date of the invention to have selected the mucoadhesive polymers recited in the instant claims based on the disclosure of the different mucoadhesive polymers disclosed by Nadh in order to optimize the delivery of the active agent, first pass metabolism, alternative routes of delivery, local modifications of tissue permeability suppression and reduction of immunogenic response, and prolonged contact time with mucosa (advantages of buccal drug delivery).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MELISSA S MERCIER whose telephone number is (571)272-9039. The examiner can normally be reached M-F 6:30 am to 4 pm EST.
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/MELISSA S MERCIER/Primary Examiner, Art Unit 1615